Comparative effectiveness of interventions for cancer treatment-related cognitive impairment in adult cancer survivors: protocol for a systematic review.

BACKGROUND: Cancer treatment-related cognitive impairment (CTRCI) can substantially reduce the quality of life of cancer survivors. Many treatments of CTRCI have been evaluated in randomized controlled trials (RCTs), including psychological interventions, pharmacologic interventions, and other therapies. There is a pressing need to establish the benefits and harms of previously studied CTRCI treatments. The proposed systematic review and network meta-analyses will assess the relative efficacy and safety of competing interventions for the management of CTRCI. METHODS: In consultation with the review team, an experienced medical information specialist will draft electronic search strategies for MEDLINE®, Embase, CINAHL, PsycINFO, and the Cochrane Trials Registry. We will seek RCTs of interventions for the treatment of CTRCI in adults with any cancer, except cancers/metastases of the central nervous system. Due to the anticipated high search yields, dual independent screening of citations will be expedited by use of an artificial intelligence/machine learning tool. The co-primary outcomes of interest will be subjective and objective cognitive function. Secondary outcomes of interest will include measures of quality of life, mental and physical health symptoms, adherence to treatment, and harms (overall and treatment-related harms and harms associated with study withdrawal), where feasible, random-effects meta-analyses and network meta-analyses will be pursued. We will address the anticipated high clinical and methodological heterogeneity through meta-regressions, subgroup analyses, and/or sensitivity analyses. DISCUSSION: The proposed systematic review will deliver a robust comparative evaluation of the efficacy and safety of existing therapies for the management of CTRCI. These findings will inform clinical decisions, identify evidence gaps, and identify promising therapies for future evaluation in RCTs.

The use of electroconvulsive therapy in special patient populations.

BACKGROUND: Despite its well-established efficacy and its increasing use, electroconvulsive therapy (ECT) remains a controversial treatment. Lack of clarity in the issues related to its use in special patient populations (for example, in children, in adolescents, in pregnant women, in the elderly, and in the medically ill) often contributes to the debate about the use of ECT. METHOD: The literature on ECT use in special patient populations is reviewed, together with the commonly associated high-risk medical conditions in clinical practice. Specific reference is made in each case to the safety, tolerability, and efficacy of the procedure. RESULTS: Much of the literature surveyed consists of case studies, although a few controlled trials are available. In general, ECT use in special populations is relatively safe and extremely effective. In small case series, ECT use in children and adolescents is effective but requires further systematic study. In pregnant women, ECT is very effective, and with proper medical care, it is relatively safe in all trimesters of pregnancy, as well as in the postpartum period. The frail elderly are particularly good candidates for ECT because they are often unresponsive to or intolerant of psychotropic medication. Medical conditions that should receive particular attention during a course of ECT are disorders of the central nervous system (CNS), cardiovascular, and respiratory system. With modern anesthesia techniques and careful medical management of each high-risk patient, most can successfully complete a course of ECT. The process of obtaining informed consent also requires special consideration in this group of patients because their capacity to consent to treatment may be compromised. CONCLUSIONS: With careful attention to each patient's medical and anesthesia needs, ECT is an effective and relatively safe procedure in high-risk special patient populations.

Apolipoprotein E polymorphism and response to electroconvulsive therapy.

The aim of this study was to determine whether the apolipoprotein E genotype differs in patients who respond or do not respond to electroconvulsive therapy (ECT). Inpatients, out-patients, and day-treatment patients who had received ECT comprised the study group. The 34 patients included met DSM-III-R criteria for affective or schizoaffective disorder. Responder or nonresponder status was assessed using the Clinical Global Inventory and Montgomery Asberg Depression Rating Scale. Blood samples were taken and coded when the patients entered the study. DNA extraction and apolipoprotein E genotyping were performed with no knowledge of the clinical classification of the patients. A significant difference in E4 genotype distribution was found between ECT responders and nonresponders (p < 0.02); psychosis was significantly less frequent in this group (p = 0.046), and there was a trend toward older onset of depression among these persons (p = 0.10). Only the E3/3 genotype was found in the patients with early-onset depression. The E4 genotype appears to define a subgroup of patients with late-onset depression who respond to ECT. If confirmed in prospective studies, this may provide a useful marker in the treatment decision-making process for late-onset depression.

A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia.

OBJECTIVE: To compare effects of risperidone with placebo (efficacy and tolerability) and haloperidol (tolerability) for treating demented patients with aggression and other behavioral symptoms. METHODS: A 13-week double-blind study involving 344 patients with dementia randomly assigned to receive placebo or flexible doses (0.5 to 4 mg/d) of risperidone or haloperidol. Behavioral symptoms were assessed by the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), the Cohen-Mansfield Agitation Inventory (CMAI), and the Clinical Global Impression (CGI) scale. Tolerability assessments included the Extrapyramidal Symptom Rating Scale, sedation levels, Functional Assessment Staging, Mini-Mental State Examination, and incidence of adverse events. RESULTS: The mean dose at endpoint was 1.1 mg/d of risperidone and 1.2 mg/d of haloperidol. Although not significant, a higher percentage of patients receiving risperidone than those receiving placebo showed clinical improvement (> or =30% reduction from baseline to endpoint in BEHAVE-AD total score) at endpoint and week 12. Reductions in the BEHAVE-AD total score were significantly greater with risperidone than with placebo at week 12. In a further analysis of aggression, the most dominant symptom in these patients, BEHAVE-AD and CMAI aggression cluster scores were significantly reduced compared with placebo at endpoint and week 12. CGI scores were also significantly reduced at endpoint and week 12. Severity of extrapyramidal symptoms with risperidone did not differ significantly from that of placebo and was less than that of haloperidol. A post hoc analysis showed significantly greater reductions in the BEHAVE-AD aggressiveness score with risperidone than haloperidol at week 12. CONCLUSION: Low-dose risperidone (mean 1.1 mg/d) was well tolerated and associated with reductions in the severity and frequency of behavioral symptoms, particularly aggression, in elderly patients with dementia.

Risperidone for the treatment of behavioral disturbances in dementia: a case series.

The authors describe a series of 22 patients with dementia and behavioral disturbances, including agitation, aggression, delusions, and hallucinations, who were treated with risperidone. Risperidone, in low doses, was well tolerated; 50% of patients experienced significant improvement, although 50% experienced some extrapyramidal symptoms.

A review of continuation and maintenance electroconvulsive therapy.

BACKGROUND: Many patients with major psychiatric disorders who are severely ill, medication-resistant, or medication-intolerant respond more reliably and quickly to a course of electroconvulsive therapy (ECT). The management of such patients after successful treatment with ECT is of significant importance given the high rate of relapse and recurrence of these disorders. The unmet clinical need to maintain the mental health of these seriously ill patients at an optimal level has revived the interest in ECT as an alternative prophylactic treatment. METHOD: We review the historical background of ECT and the literature that supports its use as a prophylactic treatment in various disorders and special populations. A clinical summary outlining its efficacy, acceptability, risks, cost-effectiveness, and medicolegal aspects is followed by a guide for prescribing ECT for prophylactic reasons. RESULTS: Continuation and maintenance ECT (C/MECT) has been found to be efficacious, safe, well tolerated, and cost-effective. Its greatest impact has been in reducing relapse, recurrence, and rehospitalization, particularly in the management of recurrent mood disorders in the elderly. The elderly are usually refractory or intolerant to pharmacotherapy but have a good response to ECT during the index episode. Parkinson's disease (PD), schizophrenia, and obsessive-compulsive disorder (OCD), as well as affective disorders coexisting with dementia, neurological disorder, or mental retardation, have also been reported to respond to C/MECT. The outcome depends greatly on rate of compliance. Cognitive risk of C/MECT need to be further studied because the literature to date consists mostly of case reports and anecdotal evidence. Controlled studies with well-defined outcome measurements are needed. CONCLUSIONS: When planning a rational approach to the care of patients with major psychiatric disorders, clinicians should carefully consider ECT along with other alternatives.

Quantitative electroencephalographic correlates of cognitive decline in normal elderly subjects.

We obtained a topographic computer analysis of the electroencephalogram in 53 normal elderly subjects. Normal aging was not associated with an increase in slow (delta) activity. However, cognitive performance correlated positively with fast (beta) activity particularly in frontal leads, even after controlling for age, education, occupation, and medication. Five subjects who showed early signs of cognitive decline, had all a marked reduction in beta activity suggesting that this may be an early indication of intellectual loss.

Four cases of progressive supranuclear palsy in patients exposed to organic solvents.

Four cases are described in which Progressive Supranuclear Palsy (PSP) is associated with the use of organic solvents. Two of them are a housewife and an exbanker who had multiple exposure to insecticides (with organic solvent base), followed years later with a diagnosis of PSP. The other two are of lithographers, both of whom worked at the same industrial firm where solvent exposure took place with subsequent development of PSP. The hypothesis that PSP is linked to an environmental toxin is supported by these cases.

Hyperammonemia in Alzheimer's disease.

Postprandial blood ammonia levels were significantly higher in 22 patients with Alzheimer's disease than in 37 control subjects. In the Alzheimer group, fasting blood ammonia levels were significantly higher in patients whose EEGs showed triphasic waves than in patients without this change. The direction of change from fasting to postprandial blood ammonia levels was also significantly different between these two groups.